Vibrational Optical Activity: From Small Chiral Molecules to Protein Pharmaceuticals and Beyond

Nafie, Laurence A.

doi:10.1016/b978-0-12-811220-5.00014-9

Cited by 14 publications

(9 citation statements)

References 203 publications

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“…Vibrational circular dichroism (VCD) spectroscopy is extremely sensitive to conformational changes. [14] As it does not rely on a few UV chromophores but on vibrational modes spanning the entire mid-infrared spectral range, [15] it is the ideal method to confirm the computationally predicted preferences and to gain deeper insights into dynamic stereochemistry of the borane ammonia complexes. [16] Figure 3a shows the experimental IR and VCD spectra of 1b recorded in CDCl 3 .…”

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confidence: 99%

Chiral Molecular Propellers of Triarylborane Ammonia Adducts

2020

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Chiral molecular propeller conformations have been induced to various triaryl structures including trityl derivatives and triaryl boranes. For borane-amine adducts, such induced propeller chirality has not been reported yet due to the low energy barrier for racemization in typical triarylboranes such as B(C 6 H 5) 3 or B(C 6 F 5) 3. Herein we demonstrate that point-chirality in side chains of chiral triarylborane-ammonia adducts, that feature intramolecular hydrogen bonds in addition to the dative N→B bond, can efficiently be transferred to triarylborane propeller chirality. Employing X-ray crystallography and both electronic and vibrational circular dichroism (ECD/VCD) spectroscopy for structural characterizations, we investigate three examples with different steric demands of the incorporated chiral alkoxyl side groups. We elucidate the conformational preferences of the molecular propellers. Furthermore, we show that computationally predicted conformational preferences obtained for the isolated, only implicitly solvated molecules are actually opposite to the experimentally observed ones.

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confidence: 99%

Chiral Molecular Propellers of Triarylborane Ammonia Adducts

2020

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“…It has become one of the most reliable choices for determining the absolute configuration and conformation of chiral molecules due to its inherent advantages, for example, richer spectral information content than ECD spectroscopy, capability of probing molecular interactions and orientation, no requirement of special chromophoric groups, and robust theoretical background ( Polyanichko et al, 2011 ; Petrovic et al, 2015 ; Kurouski, 2017 ). A large number of comprehensive reviews are available that highlighted the principle as well as applications of VCD on molecular chirality ( Nafie, 2008 ; Yang and Xu, 2010 ; Burgueño-Tapia and Joseph-Nathan, 2015 ; Kurouski, 2017 ; Nafie, 2018 ; Krupová et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…It is the inelastic counterpart of Rayleigh optical activity ( Andrews, 1980 ) and is essentially measured as the difference between the Raman scattering intensities for right and left circular polarized incident or scattered radiation. Accordingly, there are four kinds of linear ROA corresponding to each of the two circularly polarized states of incident and scattered radiation ( Collins et al, 2017 ; Nafie, 2018 ; Nafie, 2020 ). Since its first demonstration in 1973 ( Barron et al, 1973 ), it has already become a matured technique and found widespread applications in diverse fields ranging from chiral molecules to viruses ( Blanch et al, 2002 ; Blanch et al, 2003 ; Zhu et al, 2005 ; Hoffmann, 2012 ; Parchaňský et al, 2014 ; Haraguchi et al, 2015 ; Gąsior-Głogowska et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Polarimetric Measurements of Surface Chirality Based on Linear and Nonlinear Light Scattering

2021

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A molecule, molecular aggregate, or protein that cannot be superimposed on its mirror image presents chirality. Most living systems are organized by chiral building blocks, such as amino acids, peptides, and carbohydrates, and any change in their molecular structure (i.e., handedness or helicity) alters the biochemical and pharmacological functions of the molecules, many of which take place at surfaces. Therefore, studying surface chirogenesis at the nanoscale is fundamentally important and derives various applications. For example, since proteins contain highly ordered secondary structures, the intrinsic chirality can be served as a signature to measure the dynamics of protein adsorption and protein conformational changes at biological surfaces. Furthermore, a better understanding of chiral recognition and separation at bio-nanointerfaces is helpful to standardize chiral drugs and monitor the synthesis of adsorbents with high precision. Thus, exploring the changes in surface chirality with polarized excitations would provide structural and biochemical information of the adsorbed molecules, which has led to the development of label-free and noninvasive measurement tools based on linear and nonlinear optical effects. In this review, the principles and selected applications of linear and nonlinear optical methods for quantifying surface chirality are introduced and compared, aiming to conceptualize new ideas to address critical issues in surface biochemistry.

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“…A few examples, which have been reported, are shown in Scheme . Instead of publication output, the importance of VCD for the pharmaceutical industry can be measured in instrument sales numbers (nearly every major pharmaceutical company has access to a VCD instrument) or the number of patents, which cite VCD as main method for AC assignments (currently more than 130 applications and 95 patents granted). , In addition, since December 2016, VCD spectroscopy is recognized as the standard method for AC assignments in the US Pharmacopeia (USP 39-NF34, Chapters 728 and 1728). Overall, for the past decade covered by this review article, we estimate the number of AC assignments in pharmaceutical industry using VCD spectroscopy to be in the thousands.…”

Section: Introductionmentioning

confidence: 99%

Absolute Configurations of Synthetic Molecular Scaffolds from Vibrational CD Spectroscopy

2019

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Vibrational circular dichroism (VCD) spectroscopy is one of the most powerful techniques for the determination of absolute configurations (AC), as it does not require any specific UV/vis chromophores, no chemical derivatization, and no growth of suitable crystals. In the past decade, it has become increasingly recognized by chemists from various fields of synthetic chemistry such as total synthesis and drug discovery as well as from developers of asymmetric catalysts. This perspective article gives an overview about the most important experimental aspects of a VCD-based AC determination and explains the theoretical analysis. The comparison of experimental and computational spectra that leads to the final conclusion about the AC of the target molecules is described. In addition, the review summarizes unique VCD studies carried out in the period 2008−2018 that focus on the determination of unknown ACs of new compounds, which were obtained in its enantiopure form either through direct asymmetric synthesis or chiral chromatography.

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Vibrational Optical Activity: From Small Chiral Molecules to Protein Pharmaceuticals and Beyond

Cited by 14 publications

References 203 publications

Chiral Molecular Propellers of Triarylborane Ammonia Adducts

Chiral Molecular Propellers of Triarylborane Ammonia Adducts

Polarimetric Measurements of Surface Chirality Based on Linear and Nonlinear Light Scattering

Absolute Configurations of Synthetic Molecular Scaffolds from Vibrational CD Spectroscopy

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